Therapeutic efficacy of rose oil: A comprehensive review of clinical evidence.

OBJECTIVE
Rose oil is obtained from the petals of difference Rosa species especially Rosa centifolia L. and Rosa damascena Mill. Various pharmacological properties have been attributed to rose oil. The aim of the present study was to review the rose oil therapeutic effects which had been clinically evaluated in trial studies.


MATERIALS AND METHODS
Google scholar, PubMed, Cochrane Library, and Scopus were searched for human studies which have evaluated the therapeutic effects of rose oil and published in English language until August 2015.


RESULTS
Thirteen clinical trials (772 participants) were included in this review. Rose oil was administered via inhalation or used topically. Most of the studies (five trials) evaluated the analgesic effect of rose oil. Five studies evaluated the physiological relaxation effect of rose oil. Anti-depressant, psychological relaxation, improving sexual dysfunction, and anti-anxiety effects were the other clinical properties reported for rose oil.


CONCLUSION
Numerous studies on the pharmacological properties of rose oil have been done in animals, but studies in humans are few. In this study, it was observed that rose oil had physiological and psychological relaxation, analgesic and anti-anxiety effects. To obtain conclusive results on the efficacy and safety of rose oil, further clinical trials with larger sample size and better designation are required.


Introduction
Rosa species commonly known as rose (Family Rosaceae) are among the most popular and widely used medicinal plants all over the world. They are originated from the Middle East but are cultivated all over the world (Krussman, 1981). Rose oil is the essential oil extracted from the petals of Rosa species especially R. damascena and R. centifolia. Some historical evidence shows that rose oil is originated from Greece (Zargari, 1992). Currently, the main producing countries of this essential oil are Bulgaria, Turkey, and Morocco. This oil is semisolid, pale, yellow, and very expensive (Baydar, 2005).
The aim of the present study is to comprehensively review the effects of rose oil in human studies.

Methods
A literature review was performed until August 2015. We searched Pubmed, the Cochrane Library, Google scholar, and Scopus for studies evaluating the effects of rose oil in human subjects. Only, The the papers written in English were considered. The reference list from retrieved articles and review articles has been also searched. We did a Boolean search using the term "or" / "and" to explore (search by subject heading) and map (search by keyword) the MeSH headings. The search terms were: "rosa" or "rose" or "rose oil" and "volatile oil" or "essential oil" and "clinical" or "human". This search excluded case reports, comments, editorials, and letters using the Boolean operator "not" ( Figure  1).

Results
The electronic search yielded 28 items. Papers without full text, articles that were not written in English and articles that had been investigated other species of Rosa were excluded. Thirteen clinical trials (772 participants) were included. The included studies evaluated rose oil via different approaches.
Rose oil has been administered as aromatherapy or topically in these studies. It has been demonstrated that essential oils can be absorbed into the body via the skin or the olfactory system (Dye,1997;Tisserand,1996). Many studies found that olfactory stimulation by essential oils could produce instant changes in physiological parameters including muscle tension, blood pressure (BP), pulse rate, skin temperature, skin blood flow, electrodermal activity, and brain activity (Diego et al., 1998;Field et al., 2005;Lorig and Schwartz, 1988;Tisserand, 1996;Van Toller et al., 1993). Table 1 shows a summary of these studies.  Farnia et al. (2015a) showed that R. damascena oil improves the symptoms of depression and selective serotonin reuptake inhibitors-induced sexual dysfunction (SSRI-ISD) in 60 male patients who were suffering from major depressive disorder (MDD) and were being treated with SSRIs. In another similar study on 50 female patients suffered from depression and SSRI-ISD, sexual desire, sexual orgasms and sexual satisfaction increased, and pain decreased by rose oil inhalation. The effect of rose oil in improvement of sexual function in male patients was more than that in female patients (Farnia et al., 2015b). Some mechanisms have been also suggested for anti-depressant activity of rose oil including antagonistic effect on the stimulation of the post-synaptic 5-HT2 and 5-HT3 receptors as well as antagonistic effect on the cortico-limbic 5-HT receptors, which may also affect sexual behavior and could be responsible for increasing sexual desire, ejaculation, and orgasm. Moreover, rose oil increased the release of dopamine and norepinephrine in the substantia nigra, and inhibited nitric oxide synthase (Farnia et al., 2015b)

Studies focusing on analgesic effect
In addition to conventional therapy, inhalation of the fragrance of rose essential oil by eighty patients with renal colic in the emergency room, effectively reduced renal colic pain (Ayan et al., 2013).
It was found that massage with rose oil reduces the severity of primary dysmenorrhea compared to massage therapy alone in 75 students (Sadeghi AvalShahr et al., 2015). Rose oil in combination with other essential oils also showed beneficial effects in reducing menstrual pain and bleeding (Marzouk et al., 2013;Kim et al., 2011).
A double-blind placebo controlled clinical trial compared the effects of rose oil inhalation with inhalation of almond oil. The results demonstrated reduction in postoperative pain in 32 3-6-year-old children without any significant side effects (Marofi et al., 2015). The possible mechanisms for reducing pain by rose oil inhalation are stimulating the olfactory system, increasing parasympathetic activity, releasing neurotransmitters such as enkephalin and endorphin as well as reducing sympathetic activity and the release of cortisol and noradrenalin Lee et al., 2011;Park et al., 2007;Tsunetsugu et al., 2007).   Igarashi et al. (2014) showed that olfactory stimulation by rose oil induces physiological and psychological relaxation effects. In this study, the participants were exposed to air impregnated with rose oil for 90 seconds. Control subjects were in the same situation but inhaled only air that was not impregnated with rose oil. The results showed that inhalation of rose oil significantly decreases oxy-hemoglobin concentration and activity in the right prefrontal cortex and increases comfortable feeling conditions. Haze et al. (2002) found that inhalation of rose oil decreases relative sympathetic activity as measured by heart rate variability and low frequency amplitude of systolic blood pressure in healthy adult females.

Other effects
According to the Fukui et al. (2007) study rose oil inhalation decreased salivary cortisol and testosterone levels in healthy participants. Kheirkhah et al. (2014) investigated the efficacy of R. damascena oil in anxiety in the first stage of labor and showed reduction of anxiety in the active phase. Moreover, Hur et al. (2005) reported that aromatherapy with rose oil could reduce plasma epinephrine and norepinephrine, but does not have significant effect in mother's anxiety. In animal studies, two phytochemicals including sytrinol and 2-phenylethyl alcohol have been shown to be responsible for anxiolytic activity of rose oil (Burns et al., 2000;Senol et al., 2013). Hongratanaworakit (2009) showed that topical application of rose oil significantly decreases blood oxygen saturation, breathing rate, and systolic blood pressure in forty healthy subjects. In this study, olfactory stimulation by inhalation was prevented. Hur et al. (2007) in a study on 58 women showed that aromatherapy massage produces significant differences between pre and post-treatment levels of systolic blood pressure.

Conclusion
Different therapeutic properties of rose oil have been investigated in human studies and the most important of them are analgesic and anti-depressant activities. No side effects have been reported from rose oil in investigated human studies. According to Persian Medicine, some other pharmacological activities including anti-inflammatory and anti-hemorrhoidal properties have been attributed to this oil; however, no clinical trial has been focused on these activities yet. So, it is suggested to design clinical studies to evaluate these pharmacological activities. Furthermore, more research with higher populations are recommended to investigate the efficacy and safety of treatment with rose oil.

Conflict of interest
There is no conflict of interests